Liu Zhiqiang, Li Yongfeng, Li Xiaogang, Zhao Jingyuan, Wu Shihong, Wu Heshui, Gou Shanmiao
Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Mol Ther Oncolytics. 2020 Mar 29;17:21-30. doi: 10.1016/j.omto.2020.03.006. eCollection 2020 Jun 26.
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers due to frequently late diagnosis and futile treatment. It is a crucial necessity to determine the mechanisms of PDAC. Y-box Binding Protein 1 (YBX1), a highly conserved transcription factor, has been previously reported to play a role in various hallmarks of cancer. We show here that YBX1 is significantly overexpressed in PDAC and correlates with poor prognosis and reduced survival. In PDAC cell lines, YBX1 regulated cell-cycle progression, proliferation, and the expression of glycogen synthase kinase 3 beta (GSK3B) and cell-cycle-related proteins cyclin D1 and E1. Dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays established that YBX1 binds to the promoter of , suggesting that YBX1 promotes pancreatic cancer cell growth through induction of GSK3B expression. These findings offer important insights into the mechanisms underlying pathologic proliferation in PDAC.
胰腺导管腺癌（PDAC）是最致命的癌症之一，原因是其诊断常常较晚且治疗效果不佳。确定PDAC的发病机制至关重要。Y盒结合蛋白1（YBX1）是一种高度保守的转录因子，此前已有报道称其在癌症的各种特征中发挥作用。我们在此表明，YBX1在PDAC中显著过表达，且与预后不良和生存率降低相关。在PDAC细胞系中，YBX1调节细胞周期进程、增殖以及糖原合酶激酶3β（GSK3B）和细胞周期相关蛋白细胞周期蛋白D1和E1的表达。双荧光素酶报告基因和染色质免疫沉淀（ChIP）分析表明，YBX1与 的启动子结合，提示YBX1通过诱导GSK3B表达促进胰腺癌细胞生长。这些发现为PDAC病理性增殖的潜在机制提供了重要见解。
